Efficacy of pharmacotherapy for OSA in adults: a systematic review and network meta-analysis

The purpose of this systematic review and network meta-analysis is to summarize evidence on the efficacy of pharmacotherapy in adults with obstructive sleep apnea (OSA) and delineate the underlying mechanisms. Seven Databases were systematically screened for randomized controlled trials (RCTs) from their inception to September 2018. According to a pre-registered study protocol a network meta-analysis was performed to obtain intervention effects on the apnea-hypopnea-index (AHI). We identified 58 RCTs (n=1,710 patients) investigating 44 different drugs or drug-combinations. A meta-analysis of 17 trials for seven drugs versus placebo was conducted. In the network meta-analysis (I2=50%) nine drugs (tramazoline, liraglutide, spironolactone/furosemide, acetazolamide, dronabinol, zonisamide, phentermine, spironolactone, and ondansetron/fluoxetine) significantly lowered the AHI compared to placebo. Although some trials indicate favorable outcomes, these results are only valid for distinctive OSA-phenotypes or were not clinically significant. The effect sizes were small, the majority of trials were not adequately powered. There is currently insufficient evidence to recommend any pharmacotherapy for OSA and no phase-III trials are available. Future studies are advised to account for the underlying mechanisms of the intervention, as current evidence suggests that pharmacotherapy may not be a stand-alone therapy in OSA.